Optimized Extraction Process of Fu Brick Tea Polysaccharides Using Ultrasound-Assisted Enzymatic Strategy and Their Enhanced Antioxidant and Immunoprotective Activities

The immunomodulatory mechanisms of Fu brick tea polysaccharides (FBTPs) remain poorly defined, particularly regarding their structure–bioactivity relationship and the causal involvement of the gut microbiota. To address this, we investigated structurally distinct FBTPs prepared via an optimized ultrasound-assisted enzymatic extraction protocol (designated UAEPS). Characterization revealed that UAEPS possesses unique structural features, such as a lower molecular weight and higher carbohydrate content, distinguishing it from polysaccharides obtained via traditional method (HWEPS). Functionally, UAEPS exhibited potent in vitro bioactivities, including significant antioxidant, anti-inflammatory, and cytoprotective effects. In immunosuppressed mouse model, UAEPS restored immune homeostasis, attenuated multiorgan damage, and reshaped the gut microbiota, with marked enrichment of Lactobacillus . The causal role of the gut microbiota was further confirmed by a fecal microbiota transplantation experiment, where recipients mirrored the protective immunomodulatory effects. Collectively, UAEPS represents structurally distinct FBTPs whose immunomodulatory activity is mediated through gut microbiota remodeling.